It is planned to examine the possible rate limiting reactions in gluconeogenesis and ketogenesis under various physiological states. These various states will be produced by the use of diets and/or hormones. The use of liver perfusion techniques will be used in conjunction with various substrates or combination of substrates to ascertain which reactions may be rate limiting under each of these conditions. The relationship of gluconeogenesis and ketogenesis will also be examined under these various conditions to see if this relationship, as occurs in starvation and diabetes, is correlated in many other states. The possibility of metabolic compartmentalization, in addition to sub-cellular organelle compartmentalization in the liver will also be examined. Separation and the role of initiation and maintenance of "enzyme induction" will be examined by combining in vivo treatment with liver perfusion studies. The relationship of enzyme activity and metabolic potential under "optimal" conditions will also be examined in the perfused liver of animals treated various diets and/or hormones to determine if enzyme activity is limiting in the presence of excess substrate or whether other factors become important in a system as complex as the perfused liver. A study of arginine metabolism and the urea cycle particularly in regards to the in vivo synthesis of arginine and its role in metabolism such as protein synthesis and urea synthesis. These factors will include effects of diet and hormones on permeability or arginine in the liver as well as potential rate or arginine synthesis by the body.